Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients
Authors: Daniele Altomare, Frederik Barkhof, Camilla Caprioglio, Lyduine E. Collij, Philip Scheltens, Isadora Lopes Alves, Femke Bouwman, Johannes Berkhof, Ingrid S. van Maurik, Valentina Garibotto, Christian Moro, Julien Delrieu, Pierre Payoux, Laure Saint-Aubert, Anne Hitzel, José Luis Molinuevo, Oriol Grau-Rivera, Juan Domingo Gispert, Alexander Drzezga, Frank Jessen, Philip Zeyen, Agneta Nordberg, Irina Savitcheva, Vesna Jelic, Zuzana Walker, Paul Edison, Jean-François Demonet, Rossella Gismondi, Gill Farrar, Andrew W. Stephens, Giovanni B. Frisoni, Carla Abdelnour, Nuria Aguilera, Leon Aksman, Emilio Alarcón-Martín, Montse Alegret, Silvia Alonso-Lana, Daniele Altomare, Pia Andersen, Majd Arab, Malin Aspö, Ilona Bader, Ilse Bader, Nigel Banton, Frederik Barkhof, Rodrigo Barnes, Dawn Barrie, Mark Battle, Ana Belén Collado, Julie Bellet, Johannes Berkhof, Marine Biger, Cindy Birck, Gerard Bischof, Mercè Boada, Ronald Boellaard, Nenad Bogdanovic, Ariane Bollack, Stéphanie Bombois, Stefan Borg, Anne Borjesson-Hanson, Vladimir Boskov, Justine Boutantin, Claire Boutoleau-Bretonniere, Femke Bouwman, Laetitia Breuilh, Eva Bringman, Baptiste Brunel, Marco Bucci, Chris Buckley, Mar Buendía, Santi Bullich, Anna Calvet, Laia Cañada, Marta Cañada, Camilla Caprioglio, Jorge Cardoso, Jasmine Carlier, Elise Carre, Isabelle Carrie, Pascaline Cassagnaud, Emmanuelle Cassol, Miguel Castilla-Martí, Elodie Cazalon, Tiphaine Chaarriau, Rachel Chaigeau, Taylor Chalmers, Marie-Thérèse Clerc, Montserrat Clerigue, Emmanuel Cognat, Nina Coll, Lyduine E. Collij, Peter Connely, Elodie Cordier, Corine Costes, Camille Coulange, Hélène Courtemanche, Eric Creisson, Charlotte Crinquette, Rosario Cuevas, Marie-Noëlle Cufi, Sophie Dardenne, Maria de Arriba, Casper de Costa Luis, Yvonne de Gier, Delphine de Verbizier Lonjon, Veronique Dekker, Bérengère Dekyndt, Xavier Delbeuck, Julien Delrieu, Jean-François Demonet, Vincent Deramecourt, Françoise Desclaux, Carlos Diaz, Susana Diego, Mehdi Djafar, Britta Dölle, Laura Doull, Laurence Dricot, Alexander Drzezga, Bruno Dubois, Julien Dumont, Jean Dumur, Julien Dumurgier, Martin Dvorak, Mirian Ecay, Paul Edison, Claus Escher, Ainara Estanga, Ester Esteban, Guy Fanjaud, Gill Farrar, Karine Fauria, Marta Felez Sanchez, Patrick Feukam Talla, Lisa Ford, Giovanni B. Frisoni, David Fuster, Audrey Gabelle, Valentina Garibotto, Sinead Gaubert, Cédric Gauci, Christine Geldhof, Jean Georges, Joseph Ghika, Rossella Gismondi, Juan Domingo Gispert, Elena González, Valerie Goovaerts, Denis Mariano Goulart, Caroline Grasselli, Oriol Grau-Rivera, Katherine Gray, Martin Greensmith, Laure Grozn, Céline Guillemaud, Fiona Gunn, Prasad Guntur Ramkumar, Göran Hagman, Bernard Hansseuw, Fiona Heeman, Janine Hendriks, Jakob Himmelmann, Anne Hitzel, Florent Hives, Merle Hoenig, Claire Hourrègue, Justine Hudson, Jordi Huguet, Marta Ibarria, Ifrah Iidow, Sandrine Indart, Silvia Ingala, Adrian Ivanoiu, Charlotte Jacquemont, Vesna Jelic, Frank Jessen, Jieqing Jiao, Sara Jofresa, Cathrine Jonsson, Dzmitry Kaliukhovich, Silke Kern, Miia Kivipelto, Iva Knezevic, Grégory Kuchcinski, Manon Laforce, Asunción Lafuente, Françoise Lala, Adriaan Lammertsma, Michelle Lax, Thibaud Lebouvier, Ho-Yun Lee, Lean Lee, Annebet Leeuwis, Amandine Lefort, Jean-François Legrand, Mélanie Leroy, Constance Lesoil Markowski, Marcel Levy, Renaud Lhommel , Renaud Lopes, Isadora Lopes Alves, Luigi Lorenzini, Adrien Lorette, Emma Luckett, Marie Lundin, Marie-Anne Mackowiak, Vincent Malotaux, Richard Manber, Nikolay Manyakov, Pawel Markiewicz, Paula Marne, Marta Marquié, Elvira Martín, Joan Martínez, Pablo Martinez Lage, Sophie E. Mastenbroek, Aurélien Maureille, Karen Meersmans, Anja Mett, Joseph Milne, Carolina Minguillón, Marc Modat, José Luis Molinuevo, Laura Montrreal, Christian Moro, Theresa Müller, Graciela Muniz, Henk Jan Mutsarts, Ted Nilsson, Aida Ninerola, Agneta Nordberg, Wilse Novaes, Joao Nuno Carmelo Pires Silva, Greg Operto, Adela Orellana, Pierre-Jean Ousset, Olivier Outteryck, Amandine Pallardy, Alessandro Palombit, Ana Pancho, Martin Pappon, Claire Paquet, Jérémie Pariente, Florence Pasquier, Pierre Payoux, Harry Peaker, Esther Pelejà, Delphine Pennetier, Alba Pérez-Cordón, Andrés Perissinotti, Matthieu Paul Perrenoud, Sandrine Petit, Grégory Petyt, Julia Pfeil, Blanche Pirotte, Sandra Pla, Sonia Plaza Wuthrich, Lea Poitrine, Marianne Pollet, Jean-Benoit Poncelet, John Prior, Jean-Pierre Pruvo, Pauline Putallaz, Mathieu Queneau, Lisa Quenon , Andreea Rădoi, Marie Rafiq, Fiona Ramage, Maribel Ramis, Michael Reinwald, Gonzalo Rios, Craig Ritchie, Elena Rodriguez, Adeline Rollin, Olivier Rouaud, Simona Sacuiu, Laure Saint-Aubert, Arianna Sala, Anne-Sophie Salabert, Jon Saldias, Gemma Salvadó, Angela Sanabria, Lena Sannemann, Nathalie Sastre, Daniela Savina, Irina Savitcheva, Jolien Schaeverbeke, Philip Scheltens, Carine Schildermans, Mark Schmidt, Michael Schöll, Jeroen Schuermans, Franck Semah, Mahnaz Shekari, Ingmar Skoog, Oscar Sotolongo-Grau, Andrew Stephens, Tiffany Stewart, Jennyfer Stutzmann, Murray Tait, Lluis Tárraga, Juan Pablo Tartari, Ann-christine Tysen-backstrom, Sergi Valero, David Vallez Garcia, Bart N.M. van Berckel, Martijn van Essen, Koen Van Laere, Jeroen van Leur, Ingrid S. van Maurik, Rik Vandenberghe, Bruno Vellas, Jukka Virolinen, Pieter Jelle Visser, Zuzana Walker, Håkan Walles, Emilia Wallin, Grant Whitelaw, Catriona Wimberley, Zarni Win         , Alle Meije Wink, Robin Wolz, John Woodside, Maqsood Yaqub, Anna Zettergren, Philip Zeyen
Journal: JAMA Neurology (2023)

Amyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect.To assess the clinical effect of amyloid PET in memory clinic patients.The AMYPAD-DPMS is a prospective randomized clinical trial in 8 European memory clinics. Participants were allocated (using a minimization method) to 3 study groups based on the performance of amyloid PET: arm 1, early in the diagnostic workup (within 1 month); arm 2, late in the diagnostic workup (after a mean [SD] 8 [2] months); or arm 3, if and when the managing physician chose. Participants were patients with subjective cognitive decline plus (SCD+; SCD plus clinical features increasing the likelihood of preclinical Alzheimer disease), mild cognitive impairment (MCI), or dementia; they were assessed at baseline and after 3 months. Recruitment took place between April 16, 2018, and October 30, 2020. Data analysis was performed from July 2022 to January 2023.Amyloid PET.The main outcome was the difference between arm 1 and arm 2 in the proportion of participants receiving an etiological diagnosis with a very high confidence (ie, ≥90% on a 50%-100% visual numeric scale) after 3 months.A total of 844 participants were screened, and 840 were enrolled (291 in arm 1, 271 in arm 2, 278 in arm 3). Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively). After 3 months, 109 of 272 participants (40%) in arm 1 had a diagnosis with very high confidence vs 30 of 260 (11%) in arm 2 (P < .001). This was consistent across cognitive stages (SCD+: 25/84 [30%] vs 5/78 [6%]; P < .001; MCI: 45/108 [42%] vs 9/102 [9%]; P < .001; dementia: 39/80 [49%] vs 16/80 [20%]; P < .001).In this study, early amyloid PET allowed memory clinic patients to receive an etiological diagnosis with very high confidence after only 3 months compared with patients who had not undergone amyloid PET. These findings support the implementation of amyloid PET early in the diagnostic workup of memory clinic patients.EudraCT Number: 2017-002527-21.